Abstract

The transcription factor Oct4 is required in vitro for establishment and maintenance of embryonic stem cells and for reprogramming somatic cells to pluripotency. In vivo, it prevents the ectopic differentiation of early embryos into trophoblast. Here, we further explore the role of Oct4 in blastocyst formation and specification of epiblast versus primitive endoderm lineages using conditional genetic deletion. Experiments involving mouse embryos deficient for both maternal and zygotic Oct4 suggest that it is dispensable for zygote formation, early cleavage and activation of Nanog expression. Nanog protein is significantly elevated in the presumptive inner cell mass of Oct4 null embryos, suggesting an unexpected role for Oct4 in attenuating the level of Nanog, which might be significant for priming differentiation during epiblast maturation. Induced deletion of Oct4 during the morula to blastocyst transition disrupts the ability of inner cell mass cells to adopt lineage-specific identity and acquire the molecular profile characteristic of either epiblast or primitive endoderm. Sox17, a marker of primitive endoderm, is not detected following prolonged culture of such embryos, but can be rescued by provision of exogenous FGF4. Interestingly, functional primitive endoderm can be rescued in Oct4-deficient embryos in embryonic stem cell complementation assays, but only if the host embryos are at the pre-blastocyst stage. We conclude that cell fate decisions within the inner cell mass are dependent upon Oct4 and that Oct4 is not cell-autonomously required for the differentiation of primitive endoderm derivatives, as long as an appropriate developmental environment is established.

Accepted December 17, 2013.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

Other journals from The Company of Biologists

When D'Arcy Wentworth Thompson’s On Growth and Form was published 100 years ago, it raised the question of how biological forms arise during development and across evolution. In light of the advances in molecular and cellular biology since then, a succinct modern view of the question states: how do genes encode geometry? Our new special issue is packed with articles that use mathematical and physical approaches to gain insights into cell and tissue patterning, morphogenesis and dynamics, and that provide a physical framework to capture these processes operating across scales.

Read the Editorial by guest editors Thomas Lecuit and L. Mahadevan, as they provide a perspective on the influence of D'Arcy Thompson's work and an overview of the articles in this issue.

The Node currently features a number of posts to accompany the special issue. Authors of articles in the special issue talk about what On Growth and Form means to them. The creators of the commissioned cover of the special issue, Jen Ma and Matthew Spremulli, share how the cover was conceived, designed and completed. And the authors of a special issue Research Article on leaf epidermis topology reveal the extent of D’Arcy Thompson’s influence in current plant development research.

The resources pages of the Node and the BSDB have been combined and refurbished, with the new page designed to provide a range of useful links, including information on advocacy and outreach, new teaching resources for schools and databases for a wide range of species.